Article
Gastroenterology & Hepatology
Nadine N. Morgan, Lennard W. Duck, Jiongru Wu, Mahmud Rujani, Paul G. Thomes, Charles O. Elson, Peter J. Mannon
Summary: Crohn's disease patients exhibit inflammatory cytokine responses to flagellin antigens in an expanded effector memory CD4 subset that is not present in ulcerative colitis or non-inflammatory bowel disease control subjects. These cells are correlated with levels of specific anti-flagellin antibodies.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Gastroenterology & Hepatology
Guilherme Piovezani Ramos, Adebowale O. Bamidele, Emily E. Klatt, Mary R. Sagstetter, Ahmed T. Kurdi, Feda H. Hamdan, Robyn Laura Kosinsky, Joseph M. Gaballa, Asha Nair, Zhifu Sun, Surendra Dasari, Ian R. Lanza, Cody N. Rozeveld, Micah B. Schott, Guillermo Urrutia, Maria S. Westphal, Benjamin D. Clarkson, Charles L. Howe, Eric V. Marietta, David H. Luckey, Joseph A. Murray, Michelle Gonzalez, Manuel B. Braga Neto, Hunter R. Gibbons, Thomas C. Smyrk, Steven Johnsen, Gwen Lomberk, William A. Faubion
Summary: Inhibition of G9a enzyme promotes the development of regulatory T cells (Tregs) in human CD4 T cells, suggesting the potential use of G9a inhibitors for the treatment of immune-mediated diseases.
Article
Immunology
Benedikt Thelen, Vincent Schipperges, Paulina Knoerlein, Jonas F. Hummel, Frederic Arnold, Laurence Kupferschmid, Christoph S. N. Klose, Sebastian J. Arnold, Melanie Boerries, Yakup Tanriver
Summary: T-bet and Eomesodermin are T-box transcription factors that regulate type 1 immune responses in innate and adaptive lymphocytes. T-bet is the lineage-specifying transcription factor of Th1 CD4(+) T cells and controls the expression of IFN-gamma, while Eomes is less abundantly expressed and is found in CD4(+) T cells exposed to chronic antigen stimulation. A new genetic approach showed that Eomes drives a distinct transcriptional program in CD4(+) T cells that only partially overlaps with T-bet. Eomes(+) CD4(+) T cells induce the expression of IL-10 and promote a cytotoxic effector profile, suggesting that they are a unique CD4(+) T cell subset that limits inflammation and eliminates antigen-presenting and malignant cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Mark S. Lee, Peter J. Tuohy, Caleb Y. Kim, Katrina Lichauco, Heather L. Parrish, Koenraad Van Doorslaer, Michael S. Kuhns, Richard N. McLaughlin
Summary: Through evolution, purifying selection has shaped motifs in the CD4 protein that enhance its response to MHCII molecules. The importance of CD4-Lck interactions is derived from the balancing activity of an inhibitory motif, as well as motifs that direct CD4-Lck pairs to specific membrane compartments.
Article
Gastroenterology & Hepatology
Jazib Uddin, Sunil Tomar, Ankit Sharma, Lisa Waggoner, Varsha Ganesan, Sahiti Marella, Yanfen Yang, Taeko Noah, Simone Vanoni, Andrew Patterson, Chang Zeng, Paul S. Foster, Rodney Newberry, Shrinivas Bishu, John Y. Kao, Michael J. Rosen, Lee Denson, Philip D. King, Kasper Hoebe, Senad Divanovic, Ariel Munitz, Simon P. Hogan
Summary: The inhibitory receptor PIR-B plays a role in regulating CD4(+) IL17a(+) T-cell pathogenic memory responses, modulating chronic intestinal inflammatory responses and the development of colitis. The downstream axis involving PIR-B, Src-homology region 2 domain-containing phosphatase-1/2, and mammalian target of rapamycin complex 1 signaling is important for CD4(+) IL17a(+) cell survival. Furthermore, transcriptional signatures associated with Th17 cells and tissue resident memory networks were enriched in PIR-B+ murine CD4(+) T cells and human CD4(+) T cells expressing LILRB3, demonstrating the potential significance of PIR-B and its human homologue in inflammatory diseases.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Rheumatology
Lucas L. Lintermans, Coen A. Stegeman, Ernesto J. Munoz-Elias, Eric J. Tarcha, Shawn P. Iadonato, Abraham Rutgers, Peter Heeringa, Wayel H. Abdulahad
Summary: This study aimed to provide a new treatment strategy for GPA by modulating the activity of CD4(+)T(EM) cells using the specific peptide inhibitor, ShK-186. The results showed that ShK-186 reduced the expression levels of IFN gamma, TNF alpha, IL-4, IL-17, and IL-21 in CD4(+)T(H) cells from patients with GPA.
Article
Immunology
Jatin Machhi, Pravin Yeapuri, Yaman Lu, Emma Foster, Rupesh Chikhale, Jonathan Herskovitz, Krista L. Namminga, Katherine E. Olson, Mai Mohamed Abdelmoaty, Ju Gao, Rolen M. Quadros, Tomomi Kiyota, Liang Jingjing, Bhavesh D. Kevadiya, Xinglong Wang, Yutong Liu, Larisa Y. Poluektova, Channabasavaiah B. Gurumurthy, R. Lee Mosley, Howard E. Gendelman
Summary: Alzheimer's disease is characterized by pathological deposition of misfolded self-protein amyloid beta, leading to neuroinflammation. Effector T cells induced by self-antigens accelerate disease progression, suggesting a potential therapeutic target in controlling AD pathology.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Gastroenterology & Hepatology
Xianda Zhao, Ce Yuan, Dechen Wangmo, Subbaya Subramanian
Summary: This study reveals the critical role of tumor-secreted extracellular vesicles (EVs) containing microRNA miR-424 in suppressing antitumor immune response and leading to resistance to immune checkpoint blockade therapies in colorectal cancer. Modified tumor-secreted EVs with miR-424 knocked down enhance T-cell-mediated antitumor immune response and increase the efficacy of immune checkpoint blockade. Intravenous injections of modified tumor-secreted EVs induce tumor antigen-specific immune responses and boost the immune checkpoint blockade efficacy in late-stage colorectal cancer models.
Article
Oncology
Florian J. Sulzmaier, Nadja Kern, Sae Jeong Ahn, Anya Polovina, Jason Ho, Abrahim Hussain, Garrett Cyprus, Chelsie Macedo, Rajay Pandit, William Crago, Emily Rowell, John C. Timmer, Brendan P. Eckelman
Summary: INBRX-120 is a CD8 alpha-targeted Cisleukin (TM) molecule that selectively activates and expands the antitumor activity of CD8 T cells and natural killer cells without affecting regulatory T cells. It demonstrates good safety and pharmacodynamic profile.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Genetics & Heredity
Kristina Ritter, Jochen Behrends, Hanna Erdmann, Jasmin Rousseau, Alexandra Hoelscher, Johanna Volz, Immo Prinz, Thomas Lindenstrom, Christoph Hoelscher
Summary: IL-23 plays a key role in early protection against Mtb infection after vaccination, while IL-17A does not mediate this protection in the short term, but has an impact on long-term protection.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Oncology
Camilla Bove, Silvia Arcangeli, Laura Falcone, Barbara Camisa, Rita El Khoury, Beatrice Greco, Anna De Lucia, Alice Bergamini, Attilio Bondanza, Fabio Ciceri, Chiara Bonini, Monica Casucci
Summary: This study investigated the role of CD4 and CD8 T cells in CD19 CAR-T cell responses and the development of cytokine release syndrome (CRS). CD4 CAR-T cells exhibited superior proliferation and activation potential compared to CD8 CAR-T cells. CD4 CAR-T cells were found to play a key role in the development of CRS, and CD4 CAR-T cells with embedded 4-1BB were associated with a safer profile. CD4 cells were crucial for maintaining long-term responses and the combination of CD4.BBz with CD8.28z CAR-T cells resulted in the lowest toxicity without compromising antitumor efficacy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Najmeh Bozorgmehr, Isobel Okoye, Olaide Oyegbami, Lai Xu, Amelie Fontaine, Nanette Cox-Kennett, Loree M. Larratt, Mark Hnatiuk, Andrei Fagarasanu, Joseph Brandwein, Anthea C. Peters, Shokrollah Elahi
Summary: The study found that CD160 was the most upregulated co-inhibitory receptor in patients with CLL, and its expression was associated with an exhausted T cell phenotype. EVs were identified as a source of CD160 in the plasma of CLL patients. Additionally, a dominantly proinflammatory cytokine profile, especially elevated interleukin-16, was observed in CLL patients' plasma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Editorial Material
Immunology
Laura M. Snell
Summary: This study reveals a progenitor T cell subset that plays a crucial role in maintaining immune responses during chronic infection by generating effector and follicular helper T cells.
Article
Immunology
Elizabeth Robins, Ming Zheng, Qingshan Ni, Siqi Liu, Chen Liang, Baojun Zhang, Jian Guo, Yuan Zhuang, You-Wen He, Ping Zhu, Ying Wan, Qi-Jing Li
Summary: Recent research has revealed that CD4(+) and CD8(+) T cells in adaptive immunity can exhibit significant lineage plasticity, even undergoing fundamental lineage reprogramming. This shift in functional potential may suggest a new direction for HIV vaccine design.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Immunology
Devi Gunasekera, Pooja Vir, Ahmad Faisal Karim, Margaret V. Ragni, Kathleen P. Pratt
Summary: This study examined the T-cell tolerance to FVIII proteins in patients with severe hemophilia A caused by an intron 22 inversion mutation. The results showed that the proteins encoded by F8 and F8B mRNA do not induce immune responses to FVIII regions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
Emigdio D. Reyes, Katarzyna Kulej, Neha J. Pancholi, Lisa N. Akhtar, Daphne C. Avgousti, Eui Tae Kim, Daniel K. Bricker, Lynn A. Spruce, Sarah A. Koniski, Steven H. Seeholzer, Stuart N. Isaacs, Benjamin A. Garcia, Matthew D. Weitzman
MOLECULAR & CELLULAR PROTEOMICS
(2017)
Article
Immunology
Lisa Nowoslawski Akhtar, Hongwei Qin, Michelle T. Muldowney, Lora L. Yanagisawa, Olaf Kutsch, Janice E. Clements, Etty N. Benveniste
JOURNAL OF IMMUNOLOGY
(2010)
Review
Virology
Lisa Nowoslawski Akhtar, Etty N. Benveniste
JOURNAL OF VIROLOGY
(2011)
Article
Biochemistry & Molecular Biology
Susan Nozell, Travis Laver, Dorothy Moseley, Lisa Nowoslawski, Marijke DeVos, George P. Atkinson, Keith Harrison, L. Burton Nabors, Etty N. Benveniste
MOLECULAR AND CELLULAR BIOLOGY
(2008)
Review
Immunology
Brandi J. Baker, Lisa Nowoslawski Akhtar, Etty N. Benveniste
TRENDS IN IMMUNOLOGY
(2009)
Article
Microbiology
Lisa N. Akhtar, Christopher D. Bowen, Daniel W. Renner, Utsav Pandey, Ashley N. Della Fera, David W. Kimberlin, Mark N. Prichard, Richard J. Whitley, Matthew D. Weitzman, Moriah L. Szpara
Article
Microbiology
Eui Tae Kim, Joseph M. Dybas, Katarzyna Kulej, Emigdio D. Reyes, Alexander M. Price, Lisa N. Akhtar, Ann Orr, Benjamin A. Garcia, Chris Boutell, Matthew D. Weitzman
Summary: SLFN5 is identified as an ICP0 target that binds vDNA during HSV-1 Delta ICP0 infection. ICP0 mediates ubiquitination of SLFN5, leading to its degradation and repression of HSV-1 transcription. This study demonstrates that viral countermeasures can overcome SLFN antiviral activity.
NATURE MICROBIOLOGY
(2021)
Article
Microbiology
Lisa N. Akhtar, Moriah L. Szpara
CURRENT CLINICAL MICROBIOLOGY REPORTS
(2019)
Article
Clinical Neurology
L Nowoslawski, BJ Klocke, KA Roth
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2005)
Article
Multidisciplinary Sciences
R Chiesa, P Piccardo, S Dossena, L Nowoslawski, KA Roth, B Ghetti, DA Harris
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2005)